Mapping Depression in Schizophrenia: A Functional Magnetic Resonance Imaging Study

Depressive symptoms are common in schizophrenia, often left untreated, and associated with a high relapse rate, suicidal ideation, increased mortality, reduced social adjustment and poor quality of life. The neural mechanisms underlying depression in psychosis are poorly understood. Given reports of altered brain response to negative facial affect in depressive disorders, we examined brain response to emotive facial expressions in relation to levels of depression in people with psychosis. Seventy outpatients (final N = 63) and 20 healthy participants underwent functional magnetic resonance imaging during an implicit affect processing task involving presentation of facial expressions of fear, anger, happiness as well as neutral expressions and a (no face) control condition. All patients completed Beck Depression Inventory (BDI-II) and had their symptoms assessed on the Positive and Negative Syndrome Scale (PANSS). In patients, depression (BDI-II) scores associated positively with activation of the left thalamus, extending to the putamen-globus pallidus, insula, inferior-middle frontal and para-post-pre-central gyri during fearful expressions. Furthermore, patients with moderate-to-severe depression had significantly higher activity in these brain regions during fearful expressions relative to patients with no, minimal, or mild depression and healthy participants. The study provides first evidence of enhanced brain response to fearful facial expressions, which signal an uncertain source of threat in the environment, in patients with psychosis and a high level of self-reported depression.

[1]  N. Jaworska,et al.  A review of fMRI studies during visual emotive processing in major depressive disorder , 2015, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[2]  V. Kumari,et al.  Psychobiology of threat appraisal in the context of psychotic experiences: A selective review , 2015, European Psychiatry.

[3]  P. Falkai,et al.  [Depressive symptoms in schizophrenia]. , 2015, Fortschritte der Neurologie-Psychiatrie.

[4]  Peter Kirsch,et al.  Amygdala habituation: A reliable fMRI phenotype , 2014, NeuroImage.

[5]  Quan Le Van Neurophysiological study for pulvinar role in rapid detection of snakes in monkeys , 2014 .

[6]  Ó. Vilarroya,et al.  Limbic activity in antipsychotic naïve first-episode psychotic subjects during facial emotion discrimination , 2014, European Archives of Psychiatry and Clinical Neuroscience.

[7]  Jumpei Matsumoto,et al.  Pulvinar neurons reveal neurobiological evidence of past selection for rapid detection of snakes , 2013, Proceedings of the National Academy of Sciences.

[8]  Yutaka Komura,et al.  Responses of pulvinar neurons reflect a subject's confidence in visual categorization , 2013, Nature Neuroscience.

[9]  S. Frangou,et al.  Evidence of diagnostic specificity in the neural correlates of facial affect processing in bipolar disorder and schizophrenia: a meta-analysis of functional imaging studies , 2012, Psychological Medicine.

[10]  Vivien A. Casagrande,et al.  Gating and control of primary visual cortex by pulvinar , 2012, Nature Neuroscience.

[11]  Xiang Wang,et al.  Amygdala hyperactivation and prefrontal hypoactivation in subjects with cognitive vulnerability to depression , 2011, Biological Psychology.

[12]  Udo Dannlowski,et al.  Facial emotion processing in major depression: a systematic review of neuroimaging findings , 2011, Biology of Mood & Anxiety Disorders.

[13]  D. Ffytche,et al.  Neural changes following cognitive behaviour therapy for psychosis: a longitudinal study , 2011, Brain : a journal of neurology.

[14]  M. Phillips,et al.  Emotion processing in schizophrenia: fMRI study of patients treated with risperidone long-acting injections or conventional depot medication , 2011, Journal of psychopharmacology.

[15]  S. Landau,et al.  A randomised controlled trial of cognitive behaviour therapy for psychosis in a routine clinical service , 2010, Acta psychiatrica Scandinavica.

[16]  Raymond C K Chan,et al.  Facial emotion processing in schizophrenia: a meta-analysis of functional neuroimaging data. , 2010, Schizophrenia bulletin.

[17]  Ronald E. Dahl,et al.  Nothing to fear? Neural systems supporting avoidance behavior in healthy youths , 2010, NeuroImage.

[18]  Pienie Zwitserlood,et al.  Automatic Mood-Congruent Amygdala Responses to Masked Facial Expressions in Major Depression , 2010, Biological Psychiatry.

[19]  P. Fox,et al.  Amygdala hyperactivation in untreated depressed individuals , 2009, Psychiatry Research: Neuroimaging.

[20]  D. Weinberger,et al.  Changes in prefrontal and amygdala activity during olanzapine treatment in schizophrenia , 2009, Psychiatry Research: Neuroimaging.

[21]  W. Drevets,et al.  Bipolar and major depressive disorder: Neuroimaging the developmental-degenerative divide , 2009, Neuroscience & Biobehavioral Reviews.

[22]  P. Buckley,et al.  Psychiatric comorbidities and schizophrenia. , 2009, Schizophrenia bulletin.

[23]  David J McGonigle,et al.  Elsevier Editorial System(tm) for Biological Psychiatry Manuscript Draft Title: Overactivation of Fear Systems to Neutral Faces in Schizophrenia Fear of Faces in Schizophrenia in This Issue Statement Overactivation of Fear Systems to Neutral Faces in Schizophrenia , 2022 .

[24]  Julie Morris,et al.  Characterisation of depression in patients with schizophrenia. , 2008, The Indian journal of medical research.

[25]  G. Dunn,et al.  Cognitive--behavioural therapy and family intervention for relapse prevention and symptom reduction in psychosis: randomised controlled trial. , 2008, The British journal of psychiatry : the journal of mental science.

[26]  Kosha Ruparel,et al.  Limbic activation associated with misidentification of fearful faces and flat affect in schizophrenia. , 2007, Archives of general psychiatry.

[27]  H. Brückmann,et al.  Cerebral Differences in Explicit and Implicit Emotional Processing – An fMRI Study , 2007, Neuropsychobiology.

[28]  S. Zisook,et al.  Depressive symptom patterns in patients with chronic schizophrenia and subsyndromal depression , 2006, Schizophrenia Research.

[29]  G. Dunn,et al.  Understanding suicidal ideation in psychosis: findings from the Psychological Prevention of Relapse in Psychosis (PRP) trial , 2006, Acta psychiatrica Scandinavica.

[30]  T. McGlashan,et al.  Comorbid diagnoses in patients meeting criteria for the schizophrenia prodrome , 2006, Schizophrenia Research.

[31]  A. Cohen,et al.  The structure of negative symptoms within schizophrenia: implications for assessment. , 2006, Schizophrenia bulletin.

[32]  T. Sharma,et al.  Does self-perceived mood predict more variance in cognitive performance than clinician-rated symptoms in schizophrenia? , 2005, Schizophrenia bulletin.

[33]  R. Rasetti,et al.  Depressive and negative symptoms in schizophrenia: different effects on clinical features. , 2005, Comprehensive psychiatry.

[34]  Robert Ward,et al.  Response to Visual Threat Following Damage to the Pulvinar , 2005, Current Biology.

[35]  R. de Graaf,et al.  Development of depressed mood predicts onset of psychotic disorder in individuals who report hallucinatory experiences. , 2005, The British journal of clinical psychology.

[36]  R. Conley,et al.  Lifetime psychiatric symptoms in persons with schizophrenia who died by suicide compared to other means of death. , 2004, Journal of psychiatric research.

[37]  S. Rauch,et al.  Neurobiology of emotion perception II: implications for major psychiatric disorders , 2003, Biological Psychiatry.

[38]  R. Davidson,et al.  Depression: perspectives from affective neuroscience. , 2002, Annual review of psychology.

[39]  V. Schmithorst,et al.  Changes in neuronal activation with increasing attention demand in healthy volunteers: An fMRI study , 2001, Synapse.

[40]  M. Mintun,et al.  Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study , 2001, Biological Psychiatry.

[41]  E. Gordon,et al.  Event-Related Potentials to Threat-Related Faces in Schizophrenia , 2001, The International journal of neuroscience.

[42]  W. Heiden,et al.  Depression, negative symptoms, social stagnation and social decline in the early course of schizophrenia , 1999, Acta psychiatrica Scandinavica.

[43]  Karl J. Friston,et al.  How Many Subjects Constitute a Study? , 1999, NeuroImage.

[44]  S. Patten,et al.  Depression in people with first-episode schizophrenia , 1998, British Journal of Psychiatry.

[45]  R. Gur,et al.  Depression in schizophrenia: I. association with neuropsychological deficits , 1998, Biological Psychiatry.

[46]  R. Gur,et al.  Depression in schizophrenia: II. MRI and PET findings , 1998, Biological Psychiatry.

[47]  C. Gorst-Unsworth,et al.  Psychological sequelae of torture and organised violence suffered by refugees from Iraq , 1998, British Journal of Psychiatry.

[48]  A. J. Fridlund Human Facial Expression: An Evolutionary View , 1994 .

[49]  D. Stein,et al.  Negative and depressive symptoms in suicidal schizophrenics , 1994, Acta psychiatrica Scandinavica.

[50]  J. Addington,et al.  Attempted suicide and depression in schizophrenia , 1992, Acta psychiatrica Scandinavica.

[51]  E. G. Jones,et al.  A projection from the medial pulvinar to the amygdala in primates , 1976, Brain Research.

[52]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[53]  E. Bleuler [Dementia praecox or the group of schizophrenias]. , 1968, Vertex.

[54]  U. Habel,et al.  Neuronal Correlates of Facial Emotion Discrimination in Early Onset Schizophrenia , 2009, Neuropsychopharmacology.

[55]  M. Birchwood,et al.  Psychological pathways to depression in schizophrenia: studies in acute psychosis, post psychotic depression and auditory hallucinations. , 2005, European archives of psychiatry and clinical neuroscience.

[56]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[57]  P. Ekman Pictures of Facial Affect , 1976 .